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Purpose: To gather information on practices and perceptions of high-performance experts regarding their athletes' muscle fiber-type composition (MFTC) and its estimation. Methods: A questionnaire on the noninvasive versus invasive estimation of MFTC was completed by 446 experts including coaches and sport-science/sports-medicine staff. Moreover, the perceived importance of MFTC for training and performance optimization was assessed. Differences between sport types (individual and team sports) were analyzed using chi-square tests. Results: Forty percent of the experts implemented MFTC assessment in pursuit of performance optimization, while 50% did not know their athletes' MFTC but expressed a desire to implement it if they would be able to assess MFTC. Ten percent did not perceive value in MFTC assessment. Only 18% of experts believed that their athletes would undergo a muscle biopsy, leading to the adoption of alternative noninvasive techniques. Experts primarily relied on their experience to estimate MFTC (65%), with experts working in individual sports using their experience more frequently than those working in team sports (68% vs 51%; P =.009). Jump tests emerged as the second-most commonly employed method for estimating MFTC (56%). When only considering experts who are currently using MFTC, 87% use MFTC to individualize training volume and 84% to individualize training intensity. Conclusions: Experts value MFTC assessment primarily to individualize training but mainly rely on noninvasive methods to estimate MFTC. Some of these methods lack scientific validity, suggesting a continuing need for education and further research in this area. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the influence of immediate loading on the osseointegration and bone density of implants placed in a healed alveolar bone crest and supporting single crowns. Materials and Methods: Two solid titanium transmucosal mini-implants were placed in the distal regions of the mandible in 14 patients. One mini-implant was immediately functionally loaded, whereas the other was left unloaded. After 2 months of healing, biopsy samples were retrieved and the levels of new bone, old bone, and total bone (new + old) were assessed. Results: Histologic examination was performed on biopsies from 12 patients (n = 12). The new bone-to-implant contact percentage (BIC%) was 40.3% ± 16.8% and 55.1% ± 19.1% (P = .043) at the unloaded and loaded sites, respectively; in addition, the total BIC% was 44.9% ± 17.0% and 59.5% ± 18.8%, respectively (P = .034). The new bone density was 45.9% ± 11.6% for the unloaded implants and 45.9% ± 16.7% for the loaded implants (P = .622). Conclusions: Immediate loading had a positive effect on bone apposition at the implant surface, but no effect on bone density was observed after 2 months of healing. [ABSTRACT FROM AUTHOR]

Peripheral giant cell granulomas (PGCGs) are benign oral cavity tumors, reactive in nature, caused by local trauma or irritation. A 51-year-old woman presented with a soft tissue lesion related to an implant at site 36 (FDI numbering system). An excisional biopsy was completed, and the soft tissue mass was diagnosed as a PGCG. The biopsy led to a lack of keratinized tissue and vestibular depth around the implant site. After the initial healing phase, a free gingival graft was completed. Then, following soft tissue maturation, the cement-retained implant-supported prosthesis was converted into a screwretained implant-supported prosthesis that was easily accessible. With a combined periodontal and restorative approach, the KT increased, adequate vestibular depth was achieved, and there was no recurrence of the PGCG. [ABSTRACT FROM AUTHOR]

Despite the various treatments proposed with barrier membranes, one of the main challenges for guided bone regeneration (GBR) is maintaining space for large defects and ensuring an adequate blood supply. The presented feasibility case series aims to introduce an original titanium frame (TF) design, customized for each defect, as a modification of well-known principles and materials for GBR to achieve an enhanced and more predictable horizontal and vertical bone augmentation. Three patients with significant horizontal defects were treated with pre-trimmed TFs to create needed space, and then a 50/50 mixture of autograft and bovine xenograft was placed and covered with a collagen membrane. After 8 months of healing, the sites were reopened, and the titanium screws were removed with the frame. An average of 8.0 ± 1.0 mm of horizontal and 3.0 ± 0.0 mm of vertical bone gain were achieved at the time of reentry and implant placement surgery. Bone core biopsy sample was obtained during the implant placement. Histomorphometric analysis revealed that 42.8% of the sample was new vital bone, 18.8% was residual bone graft particles, and 38.4% was bone marrow-like structures. After 3 to 4 months from implant placement, the implants were restored with provisional crowns and then finalized with zirconia screw-retained crowns. This case series suggests that GBR utilizing TFs with or without collagen membranes can be considered a suitable approach for horizontal and vertical bone augmentation. However, based on only three reported cases, the results should be carefully interpreted. [ABSTRACT FROM AUTHOR]

BACKGROUND: The elastic scattering spectroscopy (ESS) device (DermaSensor Inc., Miami, FL) is a noninvasive, painless, adjunctive tool for skin cancer detection. OBJECTIVES: To investigate the performance of the ESS device in the detection of melanoma. METHODS: A prospective, investigator-blinded, multicenter study was conducted at 8 United States (US) and 2 Australian sites. All eligible skin lesions were clinically concerning for melanoma, examined with the ESS device, subsequently biopsied according to dermatologists standard of care, and evaluated with histopathology. A total of 311 participants with 440 lesions were enrolled, including 44 melanomas (63.6% in situ and 36.4% invasive) and 44 severely dysplastic nevi. RESULTS: The observed sensitivity of the ESS device for melanoma detection was 95.5% (95% CI, 84.5% to 98.8%, 42 of 44 melanomas), and the observed specificity was 32.5% (95% CI, 27.2% to 38.3%). The positive and negative predictive values were 16.0% and 98.1%, respectively. LIMITATIONS: The device was tested in a high-risk population with lesions selected for biopsy based on clinical and dermoscopic assessments of board-certified dermatologists. Most enrolled lesions were pigmented. CONCLUSION: The ESS devices high sensitivity and NPV for the detection of melanoma suggest the device may be a useful adjunctive, point-of-care tool for melanoma detection.

Introduction: The etiology of esophageal squamous papilloma (ESP) is largely unknown. Previous studies have shown a variable association with human papillomavirus (HPV) with conflicting data. The aim of this study was to further investigate the possible association of HPV in our ESP series using RNA in-situ hybridization (ISH) and compare study groups from the United States of America and China. Methods: Demographic and clinical data of patients with ESP were retrieved from the University of California Los Angeles (UCLA) (1/2016-3/2019) and Peking Union Medical College Hospital (PUMCH) (9/2014-3/2019) pathology databases. Hematoxylin and eosin slides were reexamined. Confirmed cases were examined by high- and low-risk HPV RNA ISH. Results: For the UCLA cohort, 13 429 upper endoscopies were performed and 78 biopsies from 72 patients were identified as ESP (F:M = 45:27, 66.7% > 45 years). Seventy-four (94.9%) biopsies were designated as polyps or nodules and 46.6% were located in the mid-esophagus. Other abnormal findings included gastroesophageal reflux disease (48.6%), hiatal hernia (38.9%), and esophagitis (36.1%). For the PUMCH cohort, 63 754 upper endoscopies were performed and 73 biopsies from 71 patients were identified as ESP (F:M = 48:23, 71.8% > 45 years). Sixty-four (87.7%) biopsies were designated as polyps or nodules and 57.5% were located in the mid-esophagus. Other abnormal findings included esophagitis (19.7%), and hiatal hernia (8.5%). No features of conventional cytologic dysplasia or viral cytopathic change were found. None of the cases was associated with squamous cell carcinoma, and none showed positive HPV RNA ISH results. Conclusions: No association was found between ESP and active HPV infection in our 2 cohorts. Other etiopathogenetic mechanisms, such as aging, might contribute to the development of these innocent lesions.

Purpose: To evaluate the usefulness of ridge augmentation using a customized titanium mesh (CTM) that was preformed by trimming and bending the commercial titanium mesh on a virtually reconstructed 3D acrylic resin model using clinical, radiologic, histologic, and histomorphometric analyses. Materials and Methods: This study was designed prospectively for patients who required vertical ridge augmentation using a staged approach before implant surgery. After installation of the CTM, grafting was performed using deproteinized porcine bone mineral covered with an absorbable membrane. Computed tomography was performed preoperatively and 6 months after simultaneous/staged guided bone regeneration to measure planned, reconstructed, and lacking bone volume, and the reconstruction rate was calculated based on these values. Clinical complications were also recorded, particularly the mesh exposure rate. At re-entry, the bone core was obtained using a trephine bur, and histologic and histomorphometric analyses were performed. Results: A total of 10 sites in eight patients were used for the study analysis. The mean planned bone volume was 1.15 cm3 (range: 0.78 to 1.56 cm3), mean lacking bone volume was 0.13 cm3 (range: 0 to 0.59 cm3), and mean reconstructed bone volume was 1.02 cm3 (range: 0.56 to 1.43 cm3). The exposure rate was 30% (3 out of 10 sites). The reconstruction rate was over 80%, except for one case that showed suppuration. From histomorphometric analysis, 27.52% ± 16.87% of new bone, 7.62% ± 5.19% of residual graft, and 64.86% ± 23.76% of connective tissue were observed. The core biopsy samples demonstrated different pseudoperiosteum layer appearances based on the healing stage of the augmented sites. In the premature bone, the inner osteogenic layer consisted of multiple layers of osteoblast cells with adjacent large blood vessels. However, in the mature augmented site, there was no specific inner osteogenic layer, and the outer fibrous layer was dominant. Conclusions: The fabrication of CTM based on the application of the 3D-printing technique makes vertical ridge augmentation easier and can reduce complications and achieve target bone acquisition. In addition, it is expected that quantitative analysis of the pseudoperiosteum layer will be facilitated using the CTM. [ABSTRACT FROM AUTHOR]

BACKGROUND: Excision is routinely recommended for atypical ductal hyperplasia (ADH) found on core biopsy given cancer upstage rates of near 20%. Identifying a cohort at low-risk for upstage may avoid low-value surgery. Objectives were to elucidate factors predictive of upstage in ADH, specifically near-complete core sampling, to potentially define a group at low upstage risk. PATIENTS AND METHODS: This retrospective, cross-sectional, multi-institutional study from 2015 to 2019 of 221 ADH lesions in 216 patients who underwent excision or active observation (≥ 12 months imaging surveillance, mean follow-up 32.6 months) evaluated clinical, radiologic, pathologic, and procedural factors for association with upstage. Radiologists prospectively examined imaging for lesional size and sampling proportion. RESULTS: Upstage occurred in 37 (16.7%) lesions, 25 (67.6%) to ductal carcinoma in situ (DCIS) and 12 (32.4%) to invasive cancer. Factors independently predictive of upstage were lesion size ≥ 10 mm (OR 5.47, 95% CI 2.03-14.77, p < 0.001), pathologic suspicion for DCIS (OR 12.29, 95% CI 3.24-46.56, p < 0.001), and calcification distribution pattern (OR 8.08, 95% CI 2.04-32.00, p = 0.003, regional; OR 19.28, 95% CI 3.47-106.97, p < 0.001, linear). Near-complete sampling was not correlated with upstage (p = 0.64). All three significant predictors were absent in 65 (29.4%) cases, with a 1.5% upstage rate. CONCLUSIONS: The upstage rate among 221 ADH lesions was 16.7%, highest in lesions ≥ 10 mm, with pathologic suspicion of DCIS, and linear/regional calcifications on mammography. Conversely, 30% of the cohort exhibited all low-risk factors, with an upstage rate < 2%, suggesting that active surveillance may be permissible in lieu of surgery.

Managing patients with kidney allografts largely depends on biopsy diagnosis which is based on semiquantitative assessments of rejection features and extent of acute and chronic changes within the renal parenchyma. Current methods lack reproducibility while digital image data-driven computational models enable comprehensive and quantitative assays. In this study we aimed to develop a computational method for automated assessment of histopathology transformations within the tubulointerstitial compartment of the renal cortex. Whole slide images of modified Picrosirius red-stained biopsy slides were used for the training (n = 852) and both internal (n = 172) and external (n = 94) tests datasets. The pipeline utilizes deep learning segmentations of renal tubules, interstitium, and peritubular capillaries from which morphometry features were extracted. Seven indicators were selected for exploring the intrinsic spatial interactions within the tubulointerstitial compartment. A principal component analysis revealed two independent factors which can be interpreted as representing chronic and acute tubulointerstitial injury. A K-means clustering classified biopsies according to potential phenotypes of combined acute and chronic transformations of various degrees. We conclude that multivariate analyses of tubulointerstitial morphometry transformations enable extraction of and quantification of acute and chronic components of injury. The method is developed for renal allograft biopsies; however, the principle can be applied more broadly for kidney pathology assessment.

Prostate cancer pathology plays a crucial role in clinical management but is time-consuming. Artificial intelligence (AI) shows promise in detecting prostate cancer and grading patterns. We tested an AI-based digital twin of a pathologist, vPatho, on 2603 histological images of prostate tissue stained with hematoxylin and eosin. We analyzed various factors influencing tumor grade discordance between the vPatho system and six human pathologists. Our results demonstrated that vPatho achieved comparable performance in prostate cancer detection and tumor volume estimation, as reported in the literature. The concordance levels between vPatho and human pathologists were examined. Notably, moderate to substantial agreement was observed in identifying complementary histological features such as ductal, cribriform, nerve, blood vessel, and lymphocyte infiltration. However, concordance in tumor grading decreased when applied to prostatectomy specimens (κ = 0.44) compared to biopsy cores (κ = 0.70). Adjusting the decision threshold for the secondary Gleason pattern from 5 to 10% improved the concordance level between pathologists and vPatho for tumor grading on prostatectomy specimens (κ from 0.44 to 0.64). Potential causes of grade discordance included the vertical extent of tumors toward the prostate boundary and the proportions of slides with prostate cancer. Gleason pattern 4 was particularly associated with this population. Notably, the grade according to vPatho was not specific to any of the six pathologists involved in routine clinical grading. In conclusion, our study highlights the potential utility of AI in developing a digital twin for a pathologist. This approach can help uncover limitations in AI adoption and the practical application of the current grading system for prostate cancer pathology.

This study clinically and histologically evaluated the outcome of a porcineapatite xenograft used to elevate the maxillary sinus floor in a severely atrophic ridge. A two-stage crestal window sinus elevation protocol was conducted in 24 patients with crestal bone ≤ 2 mm. Highly porous porcine carbonate apatite moistened with saline solution was placed in the elevated sinus cavity as the sole grafting material. Bone core biopsy samples were taken at 6, 9, and 12 months after sinus augmentation surgery (at implant placement). Treatment outcomes were assessed using microCT (μCT) and histologic analysis. Statistical analysis was performed using nonparametric Kruskal-Wallis test, followed by post-hoc Dunn multiple comparison test. At 6 months after implant placement, all implants achieved good primary stability (insertion torque ≥ 30 Ncm) and successfully osseointegrated. The residual graft amount (mean ± SE) was low (11.91% ± 1.99%) at 6 months and further decreased (6.11% ± 2.64%) by 12 months. On the contrary, the amount of new bone detected was 18.94% ± 4.08% at 6 months and was significantly (P < .05) increased (40.16% ± 5.27%) at 12 months. Histologic assessment revealed osteoclasts actively resorbing the graft as well as osteoblasts actively forming new bone. In the severely atrophic maxilla, the porcine-apatite xenograft promotes new bone formation while being slowly absorbed. Within the limited sample size, the porcine-apatite xenograft seems to be a good graft material for crestal window sinus augmentation. [ABSTRACT FROM AUTHOR]

Objectives: Low bone density and lack of adequate vertical bone dimension as a result of maxillary sinus pneumatization present some of the most problematic cases for endosseous implant applications in posterior maxillary regions that hinder prosthetic rehabilitation. The overall objectives of the study were to assess the histologic, histomorphometric, and radiologic evaluation of biopsies gathered from maxillary sinuses that were grafted with three different bovine bone particles (Bio-Oss, Cerabone, and Ti-Oss) and analyze the volume of the bone graft and the quantity of new bone formation. Method and materials: Thirty-six patients with < 4 mm of residual ridge height unilaterally in the posterior maxilla were equally divided into three groups, each of which received different bovine bone particles for maxillary sinus augmentation. Six months later, biopsies were harvested for histologic and histomorphometric evaluations. Volumetric changes in maxillary sinus augmentation were analyzed at 1-week and 6-month time-points following maxillary sinus augmentation surgery. Results: Histomorphometric and histologic analysis revealed a significant difference between the Ti-Oss group compared with the Bio-Oss and Cerabone groups (P=.011). In terms of residual graft particlesand soft tissue, there were no significant differences between groups. 3D volumetric reductions between 1-week (baseline) and 6-month time-points recorded significant graft volume reduction in all groups (P < .05). Significantly greater bone resorption and lower new-bone formation were manifested in the Ti-Oss group in comparison to the other groups. Conclusions: Within the limits of thisstudy, histologic and radiologic results indicated that Bio-Oss and Cerabone could be used efficiently in sinus augmentation procedures, while further prospective studies are needed to evaluate the Ti-Oss material in maxillary sinus augmentation. [ABSTRACT FROM AUTHOR]

Intestinal transplantation is the definitive treatment for intestinal failure. However, tissue rejection and graft-versus-host disease are relatively common complications, necessitating aggressive immunosuppression that can itself pose further complications. Tracking intraluminal markers in ileal effluent from standard ileostomies may present a noninvasive and sensitive way to detect developing pathology within the intestinal graft. This would be an improvement compared to current assessments, which are limited by poor sensitivity and specificity, contributing to under or over-immunosuppression, respectively, and by the need for invasive biopsies. Herein, we report an approach to reproducibly analyze ileal fluid obtained through stoma sampling for antimicrobial peptide/protein concentrations, reasoning that these molecules may provide an assessment of intestinal homeostasis and levels of intestinal inflammation over time. Concentrations of lysozyme (LYZ), myeloperoxidase (MPO), calprotectin (S100A8/A9) and β-defensin 2 (DEFB2) were assessed using adaptations of commercially available enzyme-linked immunosorbent assays (ELISAs). The concentration of α-defensin 5 (DEFA5) was assessed using a newly developed sandwich ELISA. Our data support that with proper preparation of ileal effluent specimens, precise and replicable determination of antimicrobial peptide/protein concentrations can be achieved for each of these target molecules via ELISA. This approach may prove to be reliable as a clinically useful assessment of intestinal homeostasis over time for patients with ileostomies.

PURPOSE: To assess the diagnostic performance and utility of the ExoDx IntelliScore and an OPKO4K score to predict prostate cancer in men presenting with elevated PSA-both as independent predictors and in combination with clinical/MRI characteristics. METHODS: Patients with elevated PSA were retrospectively reviewed. Abnormal tests were defined as an OPKO4K score ≥ 7.5% and an ExoDx IntelliScore ≥ 15.6. Four regression models and ROC curves were generated based on: (1) age, PSA, and DRE, (2) model 1 + OPKO4K 4Kscore ≥ 7.5%, (3) model 2 + ExoDx IntelliScore ≥ 15.6, and (4) model 3 + MRI PIRADS 4-5. RESULTS: 359 men received an OPKO4K test, 307 had MRI and 113 had ExoDx tests. 163 men proceeded to prostate biopsy and 196 (55%) were saved from biopsy. Mean age was 65.0 ± 8.7 years and mean PSA was 7.1 ± 6.1 ng/mL. Positive biopsies were found in 84 (51.5%) men. The sensitivity and negative predictive value of an OPKO4K score were 86.7% and 72.3%; values for an ExoDx test were 76.5% and 77.1%, respectively. On regression analysis, clinical markers (Age, PSA, DRE) generated an AUC of 0.559. The addition of an OPKO4K score raised the AUC to 0.653. The stepwise addition of an ExoDx score raised the AUC to 0.766. The combined use of both biomarkers, patient characteristics, and MRI yielded an AUC of 0.825. CONCLUSION: This analysis demonstrates the high negative predictive value of both the OPKO4K score and ExoDX IntelliScore independently while demonstrating that the combination of an OPKO4K score, an ExoDX IntelliScore, and MRI increases predictive capability for biopsy confirmed prostate cancer.

The field of marine mammal conservation has dramatically benefited from the rapid advancement of methods to assess the reproductive physiology of individuals and populations from steroid hormones isolated from minimally invasive skin-blubber biopsy samples. Historically, this vital information was only available from complete anatomical and physiological investigations of samples collected during commercial or indigenous whaling. Humpback whales (Megaptera novaeangliae) are a migratory, cosmopolitan species that reproduce in warm, low-latitude breeding grounds. New Caledonia is seasonally visited by a small breeding sub-stock of humpback whales, forming part of the endangered Oceania subpopulation. To better understand the demographic and seasonal patterns of reproductive physiology in humpback whales, we quantified baseline measurements of reproductive hormones (progesterone-P4, testosterone-T and 17β-estradiol-E2) using an extensive archive of skin-blubber biopsy samples collected from female humpback whales in New Caledonia waters between 2016 and 2019 (n = 194). We observed significant differences in the P4, T and E2 concentrations across different demographic groups of female humpback whales, and we described some of the first evidence of the endocrine patterns of estrous in live free-ranging baleen whales. This study is fundamental in its methodological approach to a wild species that has a global distribution, with seasonally distinct life histories. This information will assist in monitoring, managing and conserving this population as global ecological changes continue to occur unhindered.

Background & aimsPathologists quantify liver steatosis as the fraction of lipid droplet-containing hepatocytes out of all hepatocytes, whereas the magnetic resonance-determined proton density fat fraction (PDFF) reflects the tissue triacylglycerol concentration. We investigated the linearity, agreement, and correspondence thresholds between histological steatosis and PDFF across the full clinical spectrum of liver fat content associated with non-alcoholic fatty liver disease.MethodsUsing individual patient-level measurements, we conducted a systematic review and meta-analysis of studies comparing histological steatosis with PDFF determined by magnetic resonance spectroscopy or imaging in adults with suspected non-alcoholic fatty liver disease. Linearity was assessed by meta-analysis of correlation coefficients and by linear mixed modelling of pooled data, agreement by Bland-Altman analysis, and thresholds by receiver operating characteristic analysis. To explain observed differences between the methods, we used RNA-seq to determine the fraction of hepatocytes in human liver biopsies.ResultsEligible studies numbered 9 (N = 597). The relationship between PDFF and histology was predominantly linear (r = 0.85 [95% CI, 0.80-0.89]), and their values approximately coincided at 5% steatosis. Above 5% and towards higher levels of steatosis, absolute values of the methods diverged markedly, with histology exceeding PDFF by up to 3.4-fold. On average, 100% histological steatosis corresponded to a PDFF of 33.0% (29.5-36.7%). Targeting at a specificity of 90%, optimal PDFF thresholds to predict histological steatosis grades were ≥5.75% for ≥S1, ≥15.50% for ≥S2, and ≥21.35% for S3. Hepatocytes comprised 58 ± 5% of liver cells, which may partly explain the lower values of PDFF vs. histology.ConclusionsHistological steatosis and PDFF have non-perfect linearity and fundamentally different scales of measurement. Liver fat values obtained using these methods may be rendered comparable by conversion equations or threshold values.Impact and implicationsMagnetic resonance-proton density fat fraction (PDFF) is increasingly being used to measure liver fat in place of the invasive liver biopsy. Understanding the relationship between PDFF and histological steatosis fraction is important for preventing misjudgement of clinical status or treatment effects in patient care. Our analysis revealed that histological steatosis fraction is often significantly higher than PDFF, and their association varies across the spectrum of fatty liver severity. These findings are particularly important for physicians and clinical researchers, who may use these data to interpret PDFF measurements in the context of histologically evaluated liver fat content.

BackgroundIschemia-reperfusion injury (IRI) is a significant clinical concern in liver transplantation, with a key influence on short-term and long-term allograft and patient survival. Myeloid cells trigger and sustain tissue inflammation and damage associated with IRI, but the mechanisms regulating these activities are unknown. To address this, we investigated the molecular characteristics of intragraft myeloid cells present in biopsy-proven IRI- and IRI+ liver transplants.MethodsRNA-sequencing was performed on 80 pre-reperfusion and post-reperfusion biopsies from 40 human recipients of liver transplantation (23 IRI+, 17 IRI-). We used transcriptional profiling and computational approaches to identify specific gene coexpression network modules correlated with functional subsets of MPO+, lysozyme+, and CD68+ myeloid cells quantified by immunohistochemistry on sequential sections from the same patient biopsies.ResultsA global molecular map showed gene signatures related to myeloid activation in all patients regardless of IRI status; however, myeloid cell subsets differed dramatically in their spatial morphology and associated gene signatures. IRI- recipients were found to have a natural corticosteroid production and response profile from pre-reperfusion to post-reperfusion, particularly among monocytes/macrophages. The pre-reperfusion signature of IRI+ recipients included acute inflammatory responses in neutrophils and increased translation of adaptive immune-related genes in monocytes/macrophages coupled with decreased glucocorticoid responses. Subsequent lymphocyte activation at post-reperfusion identified transcriptional programs associated with the transition to adaptive immunity found only among IRI+ recipients.ConclusionsMyeloid subset-specific genes and related signaling pathways provide targets for the development of therapeutic strategies aimed at limiting IRI in the clinical setting of liver transplantation.

PURPOSE: VitreoDx is an experimental device enabling push-button collection of a neat vitreous liquid biopsy incidental to an intravitreal injection. We explored the ability of the device to collect a sample usable for proteomic biomarker discovery and testing. DESIGN: Pilot study using ex vivo human eyes. METHODS: Non-vitrectomized, human eyes from nine donors 75-91 years of age were refrigerated in BSS and used within 5 days of death. Four VitreoDx devices fitted with 25G needles, and four staked needle insulin syringes with 30G needles, were inserted at equal intervals through the pars plana of each eye and held in place by a fixture. The sampling mode of each VitreoDx device was triggered to attempt to acquire a liquid biopsy up to 70 μL. The plunger of each insulin syringe was retracted to attempt to obtain a liquid biopsy with a maximum volume of 50 μL. Samples acquired with the VitreoDx were extracted to polypropylene cryovials, refrigerated to -80 ºC, and sent for offsite proteomic analysis by proximity extension assay with a focus on panels containing approved and pipelined drug targets for neovascular disease and inflammatory factors. RESULTS: Of the attempted liquid biopsies with the novel 25G VitreoDx, 92% (66 of 72) resulted in successful acquisition (>25 μL) while 89% (64 of 72) attempted by a traditional 30G needle resulted in a successful acquisition. Sample volume sufficient for proteomics array analysis was acquired by the VitreoDx for every eye. Detectable protein was found for 151 of 166 unique proteins assayed in at least 25% of eyes sampled by VitreoDx. CONCLUSIONS: The high acquisition rate achieved by the prototype was similar to that achieved in previous clinical studies where a standard syringe was used with a 25G needle to biopsy vitreous fluid directly prior to standard intravitreal injection. Successful aspiration rates were likewise high for 30G needles. Together, these suggest that it is possible to routinely acquire liquid vitreous biopsies from patients who typically receive intravitreal injections with an injection device using a standard size needle without a vitreous cutter. Protein analysis shows that proteins of interest survive the sampling mechanism and may have potential to direct care in the future.

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease, with a worldwide prevalence of 25%. NAFLD is a spectrum that includes nonalcoholic fatty liver defined histologically by isolated hepatocytes steatosis without inflammation and nonalcoholic steatohepatitis (NASH) is the inflammatory subtype of NAFLD and is associated with disease progression, development of cirrhosis, and increased rates of liver-specific and overall mortality. The differentiation between NAFLD and NASH as well as staging NASH are important yet challenging clinical problems. Liver biopsy is currently the standard for disease diagnosis and fibrosis staging. However, this procedure is invasive, costly, and cannot be used for longitudinal monitoring. Therefore, several noninvasive quantitative imaging biomarkers have been proposed that can estimate the severity of hepatic steatosis and fibrosis. Despite this, noninvasive diagnosis of NASH and accurate risk stratification remain unmet needs. In this work, the most relevant available imaging biomarkers are reviewed and their application in patients with NAFLD are discussed.

Objectives: To understand the facilitators and barriers to the implementation of renal tumour biopsy (RTB) in the diagnostic pathway for renal tumours in England. Patients and Methods: Participants consisted of patients who had a renal tumour diagnosed and/or treated at one of five tertiary centres in England, healthcare professionals involved in the direct care of patients diagnosed with renal tumours, and clinical service managers and commissioners. The study employed a mixed‐methods research methodology consisting of individual interviews and an on‐line survey that explored the types of facilitators and barriers individuals perceived and experienced and the frequency in which these were reported. A public dissemination event took place following the completion of data collection; to facilitate discussion of potential solutions to implementing RTB. Results: There were 50 participant interviews (23 patients, 22 clinicians, and five health service commissioners/operations managers). The patient on‐line survey received 52 responses, and the clinician survey received 22 responses. Patients most frequently reported influences in choosing whether to undergo RTB pertained to wanting to know the diagnosis of their kidney mass (40%), the advice or information provided by healthcare professionals (40%), and not wishing to delay treatment (23%). Clinicians most frequently reported barriers to recommending RTB related to their uncertainty of diagnostic accuracy (56%), availability of appointments or hospital beds (52%), concerns of risk of bleeding (44%), risk of seeding (41%), and delays in meeting national cancer pathway targets (41%). The dissemination event was attended by 18 participants (seven patients and 11 clinicians). Suggestions to improve implementation included reducing variation and promotion of standardisation of practice by a consensus statement, increasing the evidence base (clinicians) and improved communication by developing better patient aids such as videos and diagrams (patients and clinicians). Conclusion: Implementation of RTB may be dependent on the quality of information provided, its format and perceived reliability of the information. Increased utilisation of RTB may be improved by development of a consensus statement on the role of biopsy, with patients expressing a preference for alternative information aids such as patient videos. [ABSTRACT FROM AUTHOR]

Summary: Background: Dietary interventions and increased physical activity are the cornerstones for management of the paediatric non‐alcoholic fatty liver disease (NAFLD). Though, no specific diet has been proven superior, Indo‐Mediterranean diet (IMD) has shown promise in adult literature. Thus, we aimed to compare the effect of IMD and a standard calorie‐restricted diet (CRD) in Indian overweight children and adolescents with biopsy‐proven NAFLD. Methods: Thirty‐nine consecutive biopsy‐proven NAFLD children between the ages of 8 and 18 years were randomized into either IMD or CRD for 180 days, and various parameters were evaluated at baseline and then after 180 days (NCT05073588). Results: A total of 34 subjects (18 in IMD and 16 in CRD group) completed the study. There was a significantly higher decrease in controlled attenuation parameter (CAP) values (as a marker of hepatic steatosis; on transient elastography) (95% CI: 4.2–73.4, p = 0.042), weight (95% CI: 0.75–5.5, p = 0.046) and body mass index (BMI) (95% CI: 0.21–2.05, p = 0.014) (but not in Pediatric NAFLD Fibrosis Index or PNFI; as a marker of hepatic fibrosis) in IMD group compared to the CRD group. Liver stiffness measurement, serum cholesterol and low‐density lipoprotein levels and HOMA‐IR decreased only in the IMD group (p < 0.001). Our statistical model showed that delta‐Weight was the only independent variable associated with delta‐CAP. Conclusion: Both IMD and CRD can improve the various anthropometric, clinical, imaging and biochemical parameters but IMD was superior to CRD in terms of reducing CAP values and weight/BMI over 180 days in overweight/obese NAFLD children. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine whether elective neck dissection can help improve outcomes in early-stage tongue and floor squamous cell carcinoma (SCC) by statistically analysing the relationship between information obtained from biopsy specimens and the incidence and prognosis of cervical lymph node metastasis (CLM). Materials and methods: Biopsy specimens of 103 patients diagnosed with early cT1–T2 cancer of the tongue and floor of the mouth were included. Results: Multivariate analysis showed that the three parameters significantly correlated with CLM, and univariate analyses showed that budding score (BS) ≥ 5 and pathological depth of invasion (pDOI) ≥ 5 mm were independent risk factors for CLM. There were significant differences in the 5-year cumulative disease-specific survival between the BS < 5 and BS ≥ 5 groups, the pDOI < 5 mm and pDOI ≥ 5 mm groups, and the positive and negative budding and depth of invasion (BD) score groups. Conclusion: In early-stage tongue and floor of the mouth cancers with maximum tumour diameter ≤ 20 mm, it may be necessary to treat occult CLM during initial surgery based on the following preoperative criteria: pDOI ≥ 5 mm or BS ≥ 5 in biopsy specimens and DOI ≥ 8 mm on imaging. The BD model exhibited the highest specificity and proved helpful for CLM prediction. Clinical relevance: pDOI ≥ 5 mm and BS ≥ 5 were independent predictors of CLM and prognosis in early-stage tongue and floor of the mouth cancers with a maximum tumour diameter of 20 mm. [ABSTRACT FROM AUTHOR]

Celiac disease (CeD) and eosinophilic esophagitis (EoE) are immune-mediated disorders that can occur in the same patient. A retrospective study at a tertiary care hospital was conducted to determine the prevalence of EoE in a pediatric population with CeD and to compare characteristics of patients with both diseases to patients with CeD-only. Among the 148 patients with CeD identified in the study, 11 patients had both CeD and EoE (7.4%). Patients with both CeD and EoE had a higher absolute eosinophil count (per μL) at diagnosis compared to patients with CeD-only (454.1 ± 122.7 vs 231.9 ± 19.4, P =.003). In conclusion, there was a higher proportion of EoE in patients with CeD than would be expected in the general population, suggesting a potential pathophysiological overlap between the 2 diseases. An elevated peripheral absolute eosinophil count may help predict which patients with CeD may additionally have EoE. [ABSTRACT FROM AUTHOR]

Objectives: This systematic review aims to assess existing research concerning the use of robotic systems to execute percutaneous lung biopsy. Methods: A systematic review was performed and identified 4 studies involving robotic systems used for lung biopsy. Outcomes assessed were operation time, radiation dose to patients and operators, technical success rate, diagnostic yield, and complication rate. Results: One hundred and thirteen robot-guided percutaneous lung biopsies were included. Technical success and diagnostic yield were close to 100%, comparable to manual procedures. Technical accuracy, illustrated by needle positioning, showed less frequent needle adjustments in robotic guidance than in manual guidance (P <.001): 2.7 ± 2.6 (range 1-4) versus 6 ± 4 (range 2-12). Procedure time ranged from comparable to reduced by 35% on average (20.1 ± 11.3 minutes vs 31.4 ± 10.2 minutes, P =.001) compared to manual procedures. Patient irradiation ranged from comparable to reduced by an average of 40% (324 ± 114.5 mGy vs 541.2 ± 446.8 mGy, P =.001). There was no significant difference in reported complications between manual biopsy and biopsies that utilized robotic guidance. Conclusion: Robotic systems demonstrate promising results for percutaneous lung biopsy. These devices provide adequate accuracy in probe placement and could both reduce procedural duration and mitigate radiation exposure to patients and practitioners. However, this review underscores the need for larger, controlled trials to validate and extend these findings. [ABSTRACT FROM AUTHOR]

Primary leiomyosarcoma of the inferior vena cava (IVC) is a rare and aggressive mesenchymal tumor, with less than 400 reported cases to date. Complete resection of the tumor with clear margins is the only proven curative treatment, providing survival benefits. Nonetheless, leiomyosarcomas in the middle segment or those extending up to it within the inferior vena cava (IVC) frequently necessitate renal reimplantation or nephrectomy, with rates varying between 56% and 75%. In this case report, we present a 65-year-old female with lower segment IVC leiomyosarcoma with middle segment extension, successfully resected and reconstructed while avoiding associated renal reimplantation or nephrectomy morbidity. [ABSTRACT FROM AUTHOR]

Background: Alport syndrome is a genetically heterogenous disorder resulting from variants in genes coding for alpha-3/4/5 chains of Collagen IV, which results in defective basement membranes in the kidney, cochlea and eye. The syndrome has different inheritance patterns and historically, was thought of as a disease affecting solely males. Case: A 15-year-old female presented with pedal oedema, hypertension and proteinuria. She underwent a kidney biopsy which showed findings in keeping with focal segmental glomerulosclerosis. Her condition was refractory to steroids. Steroid-resistant nephrotic syndrome genetics were sent, revealing a rare pathogenic variant in the COL4A5 gene. Conclusion: Heterozygous females with X-linked Alport syndrome can develop chronic kidney disease and hearing loss. Clinicians should be mindful when reviewing kidney histology to include Alport syndrome as a differential for female patients. COL4A3-5 genes should be included in all steroid-resistant nephrotic syndrome genetic panels. [ABSTRACT FROM AUTHOR]

Fanconi-Bickel syndrome (FBS) is a rare genetic disorder of carbohydrate metabolism due to pathogenic variants in SLC2A2, a gene encoding glucose transporter 2 (GLUT2), which leads to accumulation of glycogen in the kidney and liver. While consequential complex proximal tubular dysfunction is well acknowledged in the literature, long-term trajectories of kidney function in patients with FBS have not been well characterized, and kidney biopsy is performed infrequently. Here, we report on a patient with FBS followed from infancy through young adulthood who presented early on with hypercalciuria, phosphaturia, and hypophosphatemia, complicated by chronic kidney disease development during childhood. Kidney biopsy, in addition to a widespread glycogen accumulation in proximal tubular epithelial cells, demonstrated medullary nephrocalcinosis. Screening for nephrocalcinosis may be warranted in pediatric patients with FBS, along with close surveillance of their kidney function. [ABSTRACT FROM AUTHOR]

Purpose: We have previously reported that protracted Cyclooxygenase-2 (COX-2) activity in bone marrow-derived cells (BMDCs) infiltrating into biopsy wounds adjacent to the biopsy cavity of breast tumors in mice promotes M2-shift of macrophages and pro-metastatic changes in cancer cells, effects which were suppressed by oral administration of COX-2 inhibitors. Thus, local control of COX-2 activity in the biopsy wound may mitigate biopsy-induced pro-metastatic changes. Methods: A combinatorial delivery system—thermosensitive biodegradable poly(lactic acid) hydrogel (PLA-gel) incorporating celecoxib-encapsulated poly(lactic-co-glycolic acid) nanoparticles (Cx-NP/PLA-gel)—was injected into the biopsy cavity of Py230 murine breast tumors to achieve local control of COX-2 activity in the wound stroma. Results: A single intra-biopsy cavity injection of PLA-gel loaded with rhodamine-encapsulated nanoparticles (NPs) showed sustained local delivery of rhodamine preferentially to infiltrating BMDCs with minimal to no rhodamine uptake by the reticuloendothelial organs in mice. Moreover, significant reductions in M2-like macrophage density, cancer cell epithelial-to-mesenchymal transition, and blood vessel density were observed in response to a single intra-biopsy cavity injection of Cx-NP/PLA-gel compared to PLA-gel loaded with NPs containing no payload. Accordingly, intra-biopsy cavity injection of Cx-NP/PLA-gel led to significantly fewer metastatic cells in the lungs than control-treated mice. Conclusion: This study provides evidence for the feasibility of sustained, local delivery of payload preferential to BMDCs in the wound stroma adjacent to the biopsy cavity using a combinatorial delivery system to reduce localized inflammation and effectively mitigate breast cancer cell dissemination. [ABSTRACT FROM AUTHOR]

Stereotactic frameless needle brain biopsy is a common neurosurgical procedure performed via twist drill or open burr hole approaches. We aim to compare diagnostic yields and surgical outcomes to delineate the safety and efficacy of both approaches. A retrospective database of all stereotactic needle biopsy procedures performed at a single institution over 30 months was conglomerated. Demographics, medical comorbidities, operative details/complications, immediate post-operative imaging, and pathology were abstracted. Two hundred and twenty-five needle biopsies were identified, of which 165 (73.3%) were open, and 60 (26.7%) were twist drill. Diagnostic pathology yield rates between open (84.8%) and twist drill (93.3%) approaches were similar (p = 0.15), with a median of 4 cores taken in each (p = 0.30). Diagnostic tissue yields with an intra-operative pause for pathology confirmation was 90.4% compared to 79.1% without pause (p = 0.036, OR 2.49). Median operative times for open versus twist drill procedures were 68.0 min (IQR 49–83) versus 35.5 min (IQR 26–54), respectively (Wilcoxon p < 0.001), which remained significant after controlling for awaiting intraoperative pathology using bivariable linear modeling (p < 0.001). Intraoperative bleeding through the needle cannula was noted in 22 patients (9.8%), including eight twist drill (13.3%) and 14 open needles (8.5%). Of 197 cases (87.6%) with post-operative cranial imaging (CT/MRI), 90 (45.7%) demonstrated some degree of post-operative hemorrhage characterized as superficial (n = 10, 11.1%), deep/intralesional (n = 64, 71.1%) bleeding, or both (n = 16, 17.9%). Bleeding rates between open (46.7%) and twist drill (43.3%) approaches were similar (p = 0.78). Post-operative clinical decline or neurological change was noted in 9 patients (4.0%), including one twist drill (1.7%) and eight open needles (4.8%), among which 7 (78%) had deep blood products identified on post-operative imaging. Stereotactic needle biopsy via twist drill approach has similar diagnostic yield rates, asymptomatic bleeding rates, and post-operative complications with significantly shorter operative time and smaller incision size than conventional open burr hole needle biopsy. Using intra-operative frozen histopathology for presumed sufficient diagnostic tissue may improve final pathologic diagnostic rates regardless of approach technique. [ABSTRACT FROM AUTHOR]

Background: Visceral adipose tissue (VAT) abnormalities are directly associated with obesity‐associated disorders. The underlying mechanisms that confer increased pathological risk to VAT in obesity have not been fully described. Methods: A case‐control study was conducted that included 10 women with obesity (36.80 ± 7.39 years, BMI ≥ 30 kg/m2) and 10 women of normal weight (32.70 ± 9.45 years, BMI < 24.9 kg/m2). RNA was extracted from greater omentum biopsies, and, using a DNA microarray, differential transcriptomic expression of VAT in women with obesity was evaluated taking as a reference that of women with normal weight. The differentially expressed genes (DEGs) were classified into functional biological processes and signaling pathways; moreover, the protein–protein interaction (PPI) networks were integrated for a deeper analysis of the pathways and genes involved in the central obesity‐associated disorders. The expression of TNF‐α, MAPK, and AKT proteins was also quantified in VAT. Results: The VAT of women with obesity had 3808 DEGs, mainly associated with the cellular process of inflammation and carbohydrates and lipid metabolism. Overexpressed genes were associated with inflammatory, metabolic, hormonal, neuroendocrine, carcinogenic, and infectious pathways. Cellular processes related to addictive behaviors were notable. MAPK and PI3K‐AKT pathways were overexpressed, and Mapk1 and Akt3 genes were common crossing points among obesity‐associated disorders' pathways. The increased expression of MAPK, AKT, and TNF proteins was confirmed in the VAT of women with obesity. Conclusion: VAT confers a complex and blended pathogenic transcriptomic profile in obese patients, where abnormal processes are mainly controlled by activating intracellular signaling pathways that exhibit a high degree of redundancy. Identifying shared cross points between those pathways could allow specific targeting treatments to exert a widespread effect over multiple pathogenic processes. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) commonly infects immunocompromised individuals, such as cancer patients. We present a case involving a 60‐year‐old male with Stage 3A lung adenocarcinoma and chronic obstructive pulmonary disease (COPD) diagnosed with CMV tracheobronchitis, initially suspected as cancer progression. Treatment with ganciclovir led to partial improvement in symptoms of shortness of breath and cough, as well as bronchoscopic findings. However, due to ganciclovir‐induced neutropenia, the therapy was switched to foscarnet. Distinguishing between cancer progression and infectious tracheobronchitis through physical examination and chest CT scans remains challenging. In lung cancer patients presenting with airway and bronchial narrowing along with ulcerative mucosal lesions, CMV infection should be considered. A bronchoscopic biopsy is crucial for accurate diagnosis and determining the appropriate treatment in these patients. [ABSTRACT FROM AUTHOR]

Background: The prognostic significance of T-cell densities in gastric cancer (GC) was previously demonstrated in surgical resection specimens. For prognosis or response prediction, it is preferable to identify biomarkers in pre-treatment biopsies; yet, its representativeness of the tumor immune microenvironment is unclear. Objectives: This study aimed to evaluate the concordance and prognostic value of T-cell densities in paired biopsies and resections. Methods: Paired diagnostic biopsies and surgical resections were available for 131 patients with resectable GC who were treated with surgery alone in the D1/D2 trial. T-cell markers such as CD3, CD45RO, CD8, FOXP3, and Granzyme B were assessed by immunohistochemistry and digitally quantified. Tumors were categorized into high and low subgroups for each marker. The concordance between biopsies and resections was determined for each marker with Cohen's κ. To determine the prognostic value of T cells in biopsies, Cox regression was performed. Results: The concordance of T-cell high and low tumors was moderate for CD8 (κ = 0.58) and weak for other markers (κ < 0.3). CD8 and FOXP3 densities in biopsies were significantly associated with cancer-specific survival. Multivariable analysis showed that an Immunoscore incorporating CD8 and FOXP3 served as an independent prognostic marker (low vs high: hazard ratio 3.40, 95% confidence interval: 1.27–9.10; p = 0.015). Conclusion: Although the concordance in T-cell densities between biopsy and resection specimens is modest, a biopsy-based Immunoscore identified distinct biological subgroups with prognostic potential. To fully evaluate the prognostic performance of this biopsy Immunoscore, additional studies are warranted. [ABSTRACT FROM AUTHOR]

Nuclear Medicine is witnessing a revolution across a large spectrum of patient care applications, hardware, software and novel radiopharmaceuticals. We propose to offer a framework of the nuclear medicine practice of the future that incorporates multiple novelties and coined as the NEW (nu) Clear medicine. All these new developments offer a significant clarity and real clinical impact, and we need a concerted effort from all stakeholders in the field for bedside implementation and success. [ABSTRACT FROM AUTHOR]

Condyloma acuminata (CA) is a common manifestation of human papillomavirus (HPV) infection affecting the urogenital tract. While external genital lesions are frequently encountered, urethral involvement presents a therapeutic challenge due to the risk of recurrence and long-term complications such as urethral stricture. We present a case of urethral condyloma acuminata in a 43-year-old male patient who demonstrated favorable progression following electrocoagulation therapy. The patient presented with urethrorrhagia and lower urinary tract symptoms, with subsequent diagnosis confirmed via urological examination. Negative results from extensive microbiological testing supported the diagnosis. Treatment involved biopsy excision combined with electrocoagulation, resulting in complete resolution of symptoms without recurrence at 2-month follow-up. This case underscores the importance of individualized treatment strategies for intraurethral condyloma acuminata and highlights electrocoagulation therapy as a viable option with favorable outcomes. [ABSTRACT FROM AUTHOR]

Introduction/Aims Methods Results Discussion In vasculitic neuropathy (VN), it is not known whether nerve conduction studies (NCSs) showing low amplitude sensory nerve action potentials (SNAPs) or those with absent responses have a higher yield in detecting appropriate nerves for pathological confirmation. Our goal was to describe NCS findings of nerves prior to biopsy in patients with VN.We performed a retrospective study between January 2000 and April 2021 in patients with VN who either met pathological definite criteria for VN or criteria for clinically probable VN and had NCS of the sural or superficial radial sensory nerves prior to biopsy of the same nerve.We included 61 patients with VN. The pathological findings showed 37 (60.7%) definite, 14 (23%) probable, and 2 (3.3%) possible VN; eight (13%) samples did not meet Peripheral Nerve Society pathological criteria. Most patients who met definite (20 out of 37, 54%) and probable (9 out of 14, 64%) VN pathological criteria had absent SNAPs. Only three out of eight (37.5%) patients without VN pathological findings had absent SNAPs. There was no statistically significant correlation between pathological diagnosis and SNAP amplitude (χ2 = 1.98, p = .58). Additionally, no association was found between VN pathological criteria and use of immunomodulatory treatment (p = .67) or corticosteroids (p = .52).Most nerves with pathological VN findings showed no response on NCS. In patients with suspected VN, sural or superficial radial sensory nerves with absent responses on NCS are adequate biopsy targets as compared to nerves in which SNAPs can be recorded. [ABSTRACT FROM AUTHOR]

Background: Cadonilimab is the first approved dual immune checkpoint inhibitor targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), currently utilized for the treatment of various solid tumors. Oral mucosal adverse reactions, such as oral lichenoid lesions, represent one of the most prevalent immune-related adverse events associated with immune checkpoint antibodies. However, reports detailing oral side effects specifically linked to Cadonilimab are lacking. Documenting these side effects is essential to alert oncologists and stomatologists, facilitating timely intervention for affected patients. Case Presentation: We present a case involving a 35-year-old male patient diagnosed with hepatocellular carcinoma who received Cadonilimab following hepatectomy and subsequently developed extensive oral lichenoid lesions along with mucosal erosion at 13–14 weeks post-treatment initiation. A biopsy was conducted revealing immunohistochemical findings of CD3+, CD4+, CD8+, CD20 + lymphocytes, CD68 + macrophages, and α-SMA + myofibroblasts infiltrating the tissue of the oral lichenoid lesions. The patient's oral lesions improved after administration of systemic and local glucocorticoid therapy alongside cessation of Cadonilimab treatment. Conclusion: This report marks the first documented instance of an oral adverse effect associated with Cadonilimab use. It underscores that administration of this agent may lead to significant lichenoid lesions and erosions within the oral cavity—an issue warranting increased vigilance from both oncologists and stomatologists. [ABSTRACT FROM AUTHOR]

Intratumoral heterogeneity poses a significant challenge to the diagnosis and treatment of recurrent glioblastoma. This study addresses the need for non-invasive approaches to map heterogeneous landscape of histopathological alterations throughout the entire lesion for each patient. We developed BioNet, a biologically-informed neural network, to predict regional distributions of two primary tissue-specific gene modules: proliferating tumor (Pro) and reactive/inflammatory cells (Inf). BioNet significantly outperforms existing methods (p < 2e-26). In cross-validation, BioNet achieved AUCs of 0.80 (Pro) and 0.81 (Inf), with accuracies of 80% and 75%, respectively. In blind tests, BioNet achieved AUCs of 0.80 (Pro) and 0.76 (Inf), with accuracies of 81% and 74%. Competing methods had AUCs lower or around 0.6 and accuracies lower or around 70%. BioNet's voxel-level prediction maps reveal intratumoral heterogeneity, potentially improving biopsy targeting and treatment evaluation. This non-invasive approach facilitates regular monitoring and timely therapeutic adjustments, highlighting the role of ML in precision medicine. [ABSTRACT FROM AUTHOR]

The aim was to examine the acute effects of sprint exercise (SIT) on global gene expression in subcutaneous adipose tissue (AT) in healthy subjects, to enhance understanding of how SIT influences body weight regulation. The hypothesis was that SIT upregulates genes involved in mitochondrial function and fat metabolism. A total of 15 subjects performed three 30‐s all‐out sprints (SIT). Samples were collected from AT, skeletal muscle (SM) and blood (brachial artery and a subcutaneous AT vein) up to 15 min after the last sprint. Results showed that markers of oxidative stress, such as the purines hypoxanthine, xanthine and uric acid, increased markedly by SIT in both the artery and the AT vein. Purines also increased in AT and SM tissue. Differential gene expression analysis indicated a decrease in signaling for mitochondrial‐related pathways, including oxidative phosphorylation, electron transport, ATP synthesis, and heat production by uncoupling proteins, as well as mitochondrial fatty acid beta oxidation. This downregulation of genes related to oxidative metabolism suggests an early‐stage inhibition of the mitochondria, potentially as a protective mechanism against SIT‐induced oxidative stress. [ABSTRACT FROM AUTHOR]

Background: Bone scintigraphy (BS) is established as an accurate, non-invasive method for the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). In a real-life setting, however, some patients with no cardiac uptake on BS turn out to have cardiac-biopsy-confirmed ATTR-CM. We retrospectively included all patients diagnosed at the French Referral Center for ATTR-CM and who had data for BS and a cardiac biopsy. Results: Of 271 patients with positive cardiac biopsy, 14 (5%) had no cardiac uptake on 99mTc-hydroxymethylene diphosphonate BS. Cardiac uptake was found in four of the seven patients who had a second BS assessment with 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD). A retrospective review of the BS data found low cardiac uptake in four patients (two with HMDP and two with both radiotracers). Ultimately, six of the 14 patients with a biopsy-confirmed diagnosis of ATTR-CM did not show any cardiac radiotracer uptake. Conclusions: An endomyocardial biopsy may be necessary for confirming the diagnosis of ATTR-CM in patients with clinical and imaging signs of cardiac amyloidosis but no cardiac radiotracer uptake in BS. [ABSTRACT FROM AUTHOR]

AbstractTo determine the optimal variation in SUVlbm via 18F-FDG PET/CT imaging between the baseline and interim stages, and assess early response among patients with extranodal natural killer/T-cell lymphoma (ENKTCL) of 5-DS score ≥ 4, 20 patients after four cycles of chemotherapy were retrospectively enrolled and received re-biopsy targeting PET-positive residual masses. The optimal cutoff value for evaluating early response assessment was 66.75% for ΔSUVlbm%, with the area under curve of 0.985. All patients with a 5-DS score of 4 exhibited negative results upon re-biopsy. During follow-up, the median PFS of patients characterized by ΔSUVlbm% ≥66.75% and <66.75% were unreached and 10 months, respectively. Utilizing ΔSUVlbm% between baseline and interim 18F-FDG PET/CT scans can effectively identify a subset of patients who were visually analyzed as false positives(5-DS ≥ 4), which was confirmed by interim biopsy results, thus serving as a crucial indicator for early assessment of treatment outcomes in patients with ENKTCL. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and Aims Methods Results Conclusions Metabolic dysfunction‐associated steatotic liver disease (MASLD) is a growing public health problem. The secondary stage in MASLD is steatohepatitis (MASH), the co‐existence of steatosis and inflammation, a leading cause of progression to fibrosis and mortality. MASH resolution alone improves survival. Currently, MASH diagnosis is via liver biopsy. This study sought to evaluate the accuracy of imaging‐based tests for MASH diagnosis, which offer a non‐invasive method of diagnosis.Eight academic literature databases were searched and references of previous systematic reviews and included papers were checked for additional papers. Liver biopsy was used for reference standard.We report on 69 imaging‐based studies. There were 31 studies on MRI, 27 on ultrasound, five on CT, 13 on transient elastography, eight on controlled attenuation parameter (CAP) and two on scintigraphy. The pathological definition of MASH was inconsistent, making it difficult to compare studies. 55/69 studies (79.71%) were deemed high‐risk of bias as they had no preset thresholds and no validation. The two largest groups of imaging papers were on MRI and ultrasound. AUROCs were up to 0.93 for MRE, 0.90 for MRI, 1.0 for magnetic resonance spectroscopy (MRS) and 0.94 for ultrasound‐based studies.Our study found that the most promising imaging tools are MRI techniques or ultrasound‐based scores and confirmed there is potential to utilise these for MASH diagnosis. However, many publications are single studies without independent prospective validation. Without this, there is no clear imaging tool or score currently available that is reliably tested to diagnose MASH. [ABSTRACT FROM AUTHOR]

Objective: In Africa, the treatment outcomes of lupus nephritis (LN) are not well known. This is especially true in the current era where contemporary treatment options are more widely available. This retrospective study aimed to measure the outcomes of biopsy-proven LN treated at the Livingstone Tertiary Hospital (LTH) Renal Unit in Gqeberha (formerly Port Elizabeth), South Africa and to identify predictors of a poor outcome. Methods: A retrospective cohort study of 131 patients with biopsy-proven LN who had a kidney biopsy between 01 January 2012 to 31 December 2021 as identified from the biopsy register. A sub-analysis of 107 patients with proliferative and/or membranous LN was performed. Results: Mean age was 31.4 ± 12.7 years with a female predominance of 86.3%. At 6-month follow-up, 69.6% of patients had complete or partial response to treatment. This increased to 70.3% and 72.6% at 18 and 30 months, respectively. Twenty-seven patients were lost to follow-up, while 7 (5.3%) patients progressed to kidney failure (KF). There were 3 (2.3%) deaths. Predictors of poor response were an elevated baseline serum creatinine (OR = 2.53, 95% CI 0.99 – 6.52, p =.054), a decreased eGFR (OR = 2.92, 95% CI 0.94 – 9.09, p =.065) and an elevated blood pressure (OR = 6.06, 95% CI 1.11 – 33.33, p =.038) at the time of biopsy. Infections were the most common adverse event with 50 infections seen in 39 (29.8%) patients. Herpes viral infections were frequently noted (n = 12) accounting for 24.0% of all documented infections. Conclusion: Response rates were similar in this cohort when compared to other contemporary studies. Predictors of poor response were an elevated baseline serum creatinine, a decreased eGFR and an elevated blood pressure at time of the biopsy. Infections were the most common occurring adverse event, although the mortality rate remained low at 2.3%. [ABSTRACT FROM AUTHOR]

Background: The giant cell tumor of the tendon pod is a benign neoplasia that can be present in any bone or tendon pod. Its etiology is unknown. Nevertheless, it is related to a chronic inflammatory process. It usually occurs in women between the third and fifth decade as a palpable and painless mass and slow growth, although it can be deformed and lead to limb loss. Case presentation: In this report, we present the case of an 11-year-old male patient, which began on June 21, 2020, with a blunt trauma. An ultrasound was performed, reporting compatible data with synovial sarcoma. Magnetic resonance was requested, with mass evidence in soft tissues in central and planting portions. A surgical procedure with a split and biopsy of the mass was carried out. The specimen was sent to the Pathology Department, leading to a diagnosis of a giant cell tumor of the tendon pod. Conclusions: The giant cell tumor of the tendon pod is rare. However, in some cases, it is crucial to consider it as a differential diagnosis. The surgical management of this entity has proven to reduce recurrence rates. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of adjusted prostate-specific antigen density (PSADadj) in the diagnosis of prostate cancer (PCa). Methods: Data from 410 patients who underwent transrectal ultrasound-guided prostate biopsy were retrospectively analyzed in Beijing Tsinghua Changgung Hospital between November 2014 and March 2024. All patients were divided into PCa and benign prostatic hyperplasia (BPH) groups according to pathological results. Multivariate logistic regression analyses were performed to evaluate the odd ratios (ORs) of predictors for PCa occurrence. Receiver operating characteristic curves were plotted, and the area under the curve (AUC) values were used to assess and compare the diagnostic accuracies of total PSA (tPSA), free-to-total (f/t) PSA, free PSA (fPSA), PSAD, and PSADadj (PSAD×weight). Results: There were 166 patients in the PCa group and 244 in the BPH group. Multivariate analyses demonstrated that PSAD was positively correlated with the presence of PCa, with the highest OR value among all PSA-related parameters (OR = 19.075, p<0.001). tPSA, fPSAD, PSAD, and PSADadj had high accuracy in predicting PCa, with AUC values of 0.633, 0.730, 0.778, and 0.780. Of note, PSADadj had the highest AUC with a sensitivity of 63.3% and specificity of 81.6%. Similarly, in patients with a PSA level in the gray zone, the diagnostic accuracy of PSADadj in predicting PCa (AUC, 0.709; 95% CI, 0.616-0.802) remained better than other PSA-related markers. Conclusion: PSADadj has an advantage over other PSA-related markers in detecting PCa and could be used for making biopsy decisions. [ABSTRACT FROM AUTHOR]

Objective: Intracytoplasmic sperm injection (ICSI) is commonly employed in preimplantation genetic testing (PGT) to minimize the risk of foreign sperm DNA contamination. Cryopreserved embryos from patients with recurrent miscarriage or repeated implantation failure, who have undergone conventional in vitro fertilization (IVF), can be thawed and biopsied for PGT. Therefore, we aimed to assess the accuracy and effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) on frozen embryos using conventional IVF (c-IVF) insemination methods. Methods: From January 2021 to November 2023, our center conducted 107 thawed cryopreserved embryo biopsy cycles to screen for PGT-A. Among them, 58 cycles used c-IVF insemination, and 49 used ICSI insemination. Basic patient clinical information, laboratory data, PGT test results, and clinical outcome data were collected. To minimize the confounding effects of patient characteristics and embryo quality on PGT-A outcomes, clinical outcomes, and contamination assessment, these variables were included in the analysis. We then evaluated the blastocyst euploidy rate, clinical outcomes, and accuracy of PGT-A results between the two groups and analyzed potential contamination in the c-IVF insemination group. Results: A total of 320 blastocysts underwent PGT-A testing, with 179 blastocysts from c-IVF insemination and 141 from ICSI insemination. Considering participants' baseline characteristics and embryological outcomes, no significant differences were found between the two groups regarding infertility type, average age, body mass index, percentage of PGT-A indications, or quality of embryonic development. Regarding PGT-A results, all 320 biopsy samples were successfully analyzed, showing no statistical variance in chromosomal euploidy, abnormality, or mosaicism rates between the two insemination methods. No parental contamination was detected in the c-IVF insemination group. When assessing clinical outcomes, parameters such as biochemical pregnancy, clinical pregnancy, and miscarriage rates did not exhibit significant discrepancies between the two groups, and no misdiagnoses were reported during the study period. Conclusion: Embryo transfer and PGT-A results are not affected by potential parental contamination in frozen-thawed embryos conceived via c-IVF. PGT-A guided embryo transfer in thawed embryos conceived by c-IVF is a viable and clinically effective approach. [ABSTRACT FROM AUTHOR]

Background: Numerous underlying causes can lead to inflammatory breast disorders. A wide range of non-specific symptoms may be presenting symptoms, which could cause a delay in diagnosis and thus improper therapy. Studies on artificial intelligence (AI) are rapidly developing and offer a wide range of possible uses in breast imaging. Artificial intelligence-based computer-assisted diagnosis (AI-CAD) holds promise in the field of mammography. It demonstrated diagnostic performances that are equivalent to or even better than those achieved by stand-alone methods. The current work aimed to identify whether AI can improve the performance of mammography in diagnosing inflammatory breast diseases and excluding the underlying malignancy in cases resistant to treatment that may reduce the need for interventional procedures such as biopsy. Methods: Our study was a retrograde one done on 34 patients with pathologically proven inflammatory breast lesions. Results: Suppurative breast lesions gave high false positive results. This was also the case with granulomatous mastitis; while simple inflammatory lesions gave true negative results on AI interrogation. Conclusions: Artificial intelligence can be of great value in diagnosing simple inflammatory breast lesions thus following up on such lesions can usually be sufficient without asking for unneeded biopsies. On the other hand, our study showed that AI had high false positive results in suppurative lesions and granulomatous mastitis. Consequently, ultrasonography can be more reliable in their diagnosis. [ABSTRACT FROM AUTHOR]

Background: Computed tomography (CT)-guided lung biopsy is a widely used technique for the diagnosis of pulmonary lesions and with a high technical success rate and diagnostic accuracy. On the other hand, it is associated with a high risk of complications, especially pneumothorax. Various methods have been tried to reduce the incidence of pneumothorax, but no established method exists. The purpose of this study was to evaluate whether the combination of tract sealing with normal saline and rapid rollover can reduce the rate of pneumothorax and chest tube insertion after CT-guided lung biopsy. Methods: We reviewed all CT-guided lung biopsies performed at a single institution between October 2016 and December 2021. Before August 2019, no specific additional techniques were employed to mitigate complications (Group 1). In contrast, after September 2019, normal saline for tract sealing was injected during needle removal, and if pneumothorax was observed during the intervention, the patient was rolled over into the puncture-site down position immediately after needle removal (Group 2). The rate of complications was compared between the two groups. Results: 130 patients in Group 1 and 173 in Group 2 were evaluated. There was no significant difference in pneumothorax rate between the two groups (30.0% vs. 23.1%, P =.177). A chest tube was inserted in 10 of 130 patients in Group 1 and only in 1 of 173 in Group 2 (P =.001). There were no complications associated with this combinational technique. Conclusions: The combination of normal saline injection and rapid rollover significantly reduced the incidence of pneumothorax requiring chest tube insertion after CT-guided lung biopsy. Therefore, normal saline injection and rapid rollover can serve as a preventive method for severe pneumothorax in CT-guided lung biopsy. [ABSTRACT FROM AUTHOR]

Background: The majority of men referred with a raised PSA for suspected prostate cancer will receive unnecessary tertiary investigations including MRI and biopsy. Here, we compared different types of biomarkers to refine tertiary referrals and when different definitions of clinically significant cancer were used. Methods: Data and samples from 798 men referred for a raised PSA (≥ 3 ng/mL) and investigated through an MRI-guided biopsy pathway were accessed for this study. Bloods were acquired pre-biopsy for liquid biomarkers and germline DNA. Variables explored included PSA + Age (base model), free/total PSA (FTPSA), Prostate Health Index (phi), PSA density (PSAd), polygenic risk score (PRS) and MRI (≥ LIKERT 3). Different diagnostic endpoints for significant cancer (≥ grade group 2 [GG2], ≥ GG3, ≥ Cambridge Prognostic Group 2 [CPG2], ≥ CPG3) were tested. The added value of each biomarker to the base model was evaluated using logistic regression models, AUC and decision curve analysis (DCA) plots. Results: The median age and PSA was 65 years and 7.13 ng/mL respectively. Depending on definition of clinical significance, ≥ grade group 2 (GG2) was detected in 57.0% (455/798), ≥ GG3 in 27.5% (220/798), ≥ CPG2 in 61.6% (492/798) and ≥ CPG3 in 42.6% (340/798). In the pre-MRI context, the PSA + Age (base model) AUC for prediction of ≥ GG2, ≥ GG3, ≥ CPG2 and ≥ CPG3 was 0.66, 0.68, 0.70 and 0.75 respectively. Adding phi and PSAd to base model improved performance across all diagnostic endpoints but was notably better when the composite CPG prognostic score was used: AUC 0.82, 0.82, 0.83, 0.82 and AUC 0.74, 0.73, 0.79, 0.79 respectively. In contrast, neither FTPSA or PRS scores improved performance especially in detection of ≥ GG3 and ≥ CPG3 disease. Combining biomarkers did not alter results. Models using phi and PSAd post-MRI also improved performances but again benefit varied with diagnostic endpoint. In DCA analysis, models which incorporated PSAd and phi in particular were effective at reducing use of MRI and/or biopsies especially for ≥ CPG3 disease. Conclusion: Incorporating phi or PSAd can refine and tier who is referred for tertiary imaging and/or biopsy after a raised PSA test. Incremental value however varied depending on the definition of clinical significance and was particularly useful when composite prognostic endpoints are used. [ABSTRACT FROM AUTHOR]

Purpose: We investigate the histopathology of the portal vein branches and lymphatic vessels to elucidate the mechanism of atrophy of the left lateral segment (LLS) of the liver in biliary atresia (BA). Methods: LLS and right anterior segment (RAS) liver biopsy samples obtained during Kasai portoenterostomy (KPE) from ten consecutive patients with BA underwent histopathological investigation of the portal vein and lymphatic vessels using double chromogenic immunostaining for CD31/D2-40 and the hepatitis-like findings (HLF) score. Each parameter and clinical data were compared between prognostic groups. Results: HLF scores in the LLS were always higher than those in the RAS. There was no difference in portal vein and lymphatic vascular morphology, whereas the number of lymphatic vessels was correlated with the fibrotic area of all specimen areas. Left-to-right ratio of the number of lymphatic vessels was correlated with the age at KPE (r = 0.784, p = 0.007) and the pre-KPE CRP value (r = 0.723, p = 0.018). Conclusions: Lymphangiogenesis on the LLS compared to the RAS was significantly correlated with the degree of fibrosis and the age at KPE. Further investigation is warranted to clarify the causes of LLS atrophy and lymphangiogenesis relevant to immune dysregulation. [ABSTRACT FROM AUTHOR]